Efficacy of ravuconazole in a murine model of vaginitis by Candida albicans / Eficacia del ravuconazol en un modelo murino de vaginitis por Candida albicans

Background. The incidence of vulvovaginal candidiasis, a common infection among healthy women primarily caused by the yeast Candida albicans, has increased significantly in recent years. Aims. The purpose of this study was to compare the efficacy of ravuconazole (RVC) and fluconazole (FLC) in the treatment of experimental C. albicans vaginitis. Methods. Forty isolates of C. albicans were screened for their in vitro susceptibility to RVC and FLC. A strain of C. albicans that was resistant to FLC (minimum inhibitory concentration [MIC] of >64 μg/ml) was selected for the in vivo study. Treatment regimens for the murine vaginal infection model were (1) 1, 5, 10, and 20 mg/kg RVC once daily, (2) 20 mg/kg RVC twice daily, (3) 20 mg/kg FLC once daily, and (4) 20 mg/kg FLC twice daily. Results. The geometric means of the MIC values at 48 h for all isolates tested were 0.05 and 0.5 μg/ml for RVC and FLC, respectively. Regimens of either RVC or FLC at 20 mg/kg twice daily were more effective to reduce the load of FLC-resistant C. albicans than single dose administration. Conclusions. Complete eradication of C. albicans from the vagina was not observed with RVC or FLC treatment in the animal model, although RVC treatment showed a lower fungal concentration 14 days after drug administration (AU)

Antecedentes. En los últimos años, ha aumentado sustancialmente la incidencia de candidiasis vulvovaginal, una infección frecuente entre mujeres sanas, causada sobre todo por la levadura Candida albicans. Objetivos. El objetivo del presente estudio fue comparar la eficacia del ravuconazol (RVC) y del fluconazol (FLC) en el tratamiento de la vaginitis experimental inducida por C. albicans. Métodos. Se examinó la sensibilidad in vitro de 40 aislamientos de C. albicans frente a RVC y FLC. Para el estudio in vivo se seleccionó una cepa de C. albicans que fue resistente a FLC (concentración inhibitoria mínima [CIM] >64 μg/ml). Las pautas de tratamiento para el modelo murino de infección vaginal fueron 1) 1, 5, 10 y 20 mg/kg de RVC una vez al día, 2) 20 mg/kg de RVC dos veces al día, 3) 20 mg/de FLC una vez al día, y 4) 20 mg/kg de FLC dos veces al día. Resultados. Para todos los aislamientos las medias geométricas de los valores de la CIM a las 48 h fueron de 0,05 y 0,5 μg/ml para RVC y FLC, respectivamente. Las pautas de 20 mg/kg de RVC o FLC dos veces al día fueron más eficaces para reducir la carga infectiva de C. albicans resistente a FLC que las administradas una vez al día. Conclusiones. En el modelo animal no se eliminó completamente C. albicans del tracto vaginal estéril mediante tratamiento con RVC o FLC. Sin embargo, el tratamiento con RVC derivó en concentraciones fúngicas más bajas 14 días después de su administración (AU)

Murine model of disseminated fusariosis: evaluation of the fungal burden by traditional CFU and quantitative PCR.

Systemic disease is the most severe clinical form of fusariosis, and the treatment involves a challenge due to the refractory response to antifungals. Treatment for murine Fusarium solani infection has been described in models that employ CFU quantitation in organs as a parameter of therapeutic efficacy. However, CFU counts do not precisely reproduce the amount of cells for filamentous fungi such as F. solani. In this study, we developed a murine model of disseminated fusariosis and compared the fungal burden with two methods: CFU and quantitative PCR. ICR and BALB/c mice received an intravenous injection of 1 × 10(7) conidia of F. solani per mouse. On days 2, 5, 7, and 9, mice from each mice strain were killed. The spleen and kidneys of each animal were removed and evaluated by qPCR and CFU determinations. Results from CFU assay indicated that the spleen and kidneys had almost the same fungal burden in both BALB/c and ICR mice during the days of the evaluation. In the qPCR assay, the spleen and kidney of each mouse strain had increased fungal burden in each determination throughout the entire experiment. The fungal load determined by the qPCR assay was significantly greater than that determined from CFU measurements of tissue. qPCR could be considered as a tool for quantitative evaluation of fungal burden in experimental disseminated F. solani infection.